tbuckley/cabot-search huggingface dataset:
The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response
Authors: Jacob E. Berchuck, Elio Adib, Sarah Abou Alaiwi, Amit K. Dash, Jin Na Shin, Dallin Lowder, Collin McColl, Patricia Castro, Ryan Carelli, Elisa Benedetti, Jenny Deng, Matthew Robertson, Sylvan C. Baca, Connor Bell, Heather M. McClure, Talal El Zarif, Matthew P. Davidsohn, Gitanjali Lakshminarayanan, Kinza Rizwan, Darlene G. Skapura, Sandra L. Grimm, Christel M. Davis, Erik A. Ehli, Kaitlin M. Kelleher, Ji-Heui Seo, Nicholas Mitsiades, Cristian Coarfa, Mark M. Pomerantz, Massimo Loda, Michael Ittmann, Matthew L. Freedman, Salma Kaochar
Journal: Cancer Research (2022)

African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and increased lipid levels in AA prostate cancer. In a metastatic prostate cancer cohort, upregulated lipid metabolism associated with poor prognosis. These findings offer the first insights into ancestry-specific differences in the prostate cancer AR cistrome. The data suggest a model whereby increased androgen signaling may contribute to higher levels of lipid metabolism, immune response, and cytokine signaling in AA prostate tumors. Given the association of upregulated lipogenesis with prostate cancer progression, our study provides a plausible biological explanation for the higher incidence and aggressiveness of prostate cancer observed in AA men.
Multivitamins and Supplements—Benign Prevention or Potentially Harmful Distraction?
Authors: Jenny Jia, Natalie A. Cameron, Jeffrey A. Linder
Journal: JAMA (2022)

More than half of adults take dietary supplements, and use of supplements in the US is projected to increase.1,2 In 2021, people in the US spent an estimated almost $50 billion on dietary supplements and the dietary supplement industry spent about $900 million on marketing.2
Patient Symptoms and Stress Testing After Elective Percutaneous Coronary Intervention in the Veterans Affairs Health Care System
Authors: Vinay Kini, Monica Parks, Wenhui Liu, Stephen W. Waldo, P. Michael Ho, Steven M. Bradley, Paul L. Hess
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Up to 60% of patients in the US receive a stress test within 2 years of percutaneous coronary intervention (PCI), prompting concerns about the possible overuse of stress testing. <h3>Objective</h3> To examine the proportion of patients who underwent stress testing within 2 years of elective PCI, proportion of patients who had symptoms that were consistent with coronary artery disease (CAD), timing of stress testing, and site-level variation in stress testing among symptomatic and asymptomatic patients. <h3>Design, Setting, and Participants</h3> This cohort study used administrative claims data and clinical records from the US Department of Veterans Affairs (VA) Clinical Assessment, Reporting, and Tracking program. Patients who underwent stress testing within 2 years of elective PCI for stable CAD between November 1, 2013, and October 31, 2015, at 64 VA facilities were included in the analysis. Patients who received stress testing for staging purposes, cardiac rehabilitation evaluation, or preoperative testing before high-risk surgery were excluded. Data were analyzed from June to December 2020. <h3>Main Outcomes and Measures</h3> The main outcome was the proportion of patients who underwent stress testing and had symptoms that were consistent with obstructive CAD, using definitions from the 2013 clinical practice guideline (Multimodality Appropriate Use Criteria for the Detection and Risk Assessment of Stable Ischemic Heart Disease). Secondary outcomes were the timing of stress testing (assessed using a cumulative incidence curve) and site-level variation in stress testing (assessed using multilevel logistic regression models). <h3>Results</h3> A total of 3705 consecutive patients (mean [SD] age 66.3 [7.6] years; 3656 men [98.7%]; 437 Black individuals [11.8%], 3175 White individuals [85.7%], and 93 individuals [2.5%] of other races and ethnicities [Asian, Hispanic or Latinx, or unknown]) had elective PCI. Of these patients, 916 (24.7%) received a stress test within 2 years, among whom 730 (79.7%) had symptoms that were consistent with obstructive CAD at the time of stress testing. Visual inspection of a cumulative incidence curve for stress testing showed no rapid increases in stress testing at 6 months or 1 year after PCI, which might coincide with routine clinical visits. The proportion of symptomatic patients who underwent stress testing at each VA site ranged from 67.7% to 100%, with no significant site-level variation in stress testing. <h3>Conclusions and Relevance</h3> Results of this study suggest that most veterans who underwent stress testing within 2 years after elective PCI had symptoms that were consistent with obstructive CAD. Therefore, measuring low-value stress testing using only administrative claims data may overestimate its prevalence, and concerns about overuse of post-PCI stress testing may be overstated.
Mortality Risk After Pediatric Tonsillectomy
Authors: Romaine F. Johnson, Ron B. Mitchell
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Options for Detecting Risk of Aminoglycoside-Induced Ototoxicity in Neonates—Reply
Authors: John H. McDermott, William G. Newman
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Dietary Supplement Sellers Receive Warnings
Authors: Rita Rubin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma Treated With Targeted Therapies
Authors: Dong-Yi Chen, Jia-Rou Liu, Chi-Nan Tseng, Ming-Jer Hsieh, Cheng-Keng Chuang, See-Tong Pang, Shao-Wei Chen, I-Chang Hsieh, Pao-Hsien Chu, Jen-Shi Chen, John Wen-Cheng Chang, Wen-Kuan Huang, Lai-Chu See
Journal: JACC CardioOncology (2022)
Predictors of hematologic response and survival with stem cell transplantation in <scp>AL</scp> amyloidosis: A 25‐year longitudinal study
Authors: Joshua N. Gustine, Andrew Staron, Raphael E. Szalat, Lisa M. Mendelson, Tracy Joshi, Frederick L. Ruberg, Omar Siddiqi, Deepa M. Gopal, Camille V. Edwards, Andrea Havasi, Michelle Kaku, K. H. Vincent Lau, John L. Berk, J. Mark Sloan, Vaishali Sanchorawala
Journal: American Journal of Hematology (2022)

High-dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long-term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was achieved by 39% of patients. The median duration of hematologic CR was 12.3 years, and 45% of patients with a hematologic CR had no evidence of a recurrent plasma cell dyscrasia at 15 years after HDM/SCT. With a median follow-up interval of 8 years, the median event-free survival (EFS) and overall survival (OS) were 3.3 and 7.6 years, respectively. Patients with a hematologic CR had a median OS of 15 years, and 30% of these patients survived >20 years. On multivariable analysis, dFLC >180 mg/L and BM plasma cells >10% were independently associated with shorter EFS, whereas BNP >81 pg/mL, troponin I > 0.1 ng/mL, and serum creatinine >2.0 mg/dL were independently associated with shorter OS. We developed a prognostic score for EFS, which incorporated dFLC >180 mg/L and BMPC% >10% as adverse risk factors. Patients with low-risk (0 factors), intermediate-risk (1 factor), and high-risk (2 factors) disease had median EFS estimates of 5.3, 2.8, and 1.0 years, respectively (p < .001). The 100-day treatment-related mortality rate was 3% in the latest treatment period (2012-2021), and the 25-year risk of t-MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis.
Combination Therapies for Advanced Hepatocellular Carcinoma: Biomarkers and Unmet Needs
Authors: Sarah Cappuyns, Josep M. Llovet
Journal: Clinical Cancer Research (2022)

Summary The novel combination of checkpoint inhibitors targeting the PD(L)1 pathway and anti-VEGFA therapy has revolutionized the treatment landscape of advanced hepatocellular carcinoma (HCC). However, biomarkers predictive of response to these therapies are still lacking, representing a major clinical challenge. See related articles by Zhang et al., p. 3499, and Zhu et al., p. 3537
Navigating to Kidney Health Equity
Authors: Derek M. Griffith, Ebele M. Umeukeje
Journal: Journal of the American Society of Nephrology (2022)

In recent years, all health organizations and institutions have agreed, in principle, that reaching health equity is important. And yet, in practice, achieving this goal is like planning a journey to a destination we are unsure exists. Typically, the goals and objectives that guide programmatic,
Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials
Authors: Jasmohan S Bajaj, Tarek I Hassanein, Nikolaos T Pyrsopoulos, Arun J Sanyal, Robert S Rahimi, Zeev Heimanson, Robert J Israel, Don C Rockey
Journal: Clinical Gastroenterology and Hepatology (2022)
Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma
Authors: Joseph J. Noh, Young-Jae Cho, Ji-Yoon Ryu, Jung-Joo Choi, Jae Ryoung Hwang, Ju-Yeon Choi, Jeong-Won Lee
Journal: Clinical Cancer Research (2022)

Abstract Purpose: To evaluate the anticancer effects of cabozantinib, temozolomide, and their combination in uterine sarcoma cell lines and mouse xenograft models. Experimental Design: Human uterine sarcoma cell lines (SK-LMS-1, SK-UT-1, MES-SA, and SKN) were used to evaluate the anticancer activity of cabozantinib, temozolomide, and their combination. The optimal dose of each drug was determined by MTT assay. Cell proliferation and apoptosis were assessed 48 and 72 hours after the drug treatments. The tumor weights were measured in an SK-LMS-1 xenograft mouse model and a patient-derived xenograft (PDX) model of leiomyosarcoma treated with cabozantinib, temozolomide, or both. Results: Given individually, cabozantinib and temozolomide each significantly decreased the growth and viability of cells. This inhibitory effect was more pronounced when cabozantinib (0.50 μmol/L) and temozolomide (0.25 or 0.50 mmol/L) were co-administered (P &amp;lt; 0.05). The combination of the drugs also significantly increased apoptosis in all cells. Moreover, this effect was consistently observed in patient-derived leiomyosarcoma cells. In vivo studies with SK-LMS-1 cell xenografts and the PDX model with leiomyosarcoma demonstrated that combined treatment with cabozantinib (5 mg/kg/d, per os administration) and temozolomide (5 mg/kg/d, per os administration) synergistically decreased tumor growth (both P &amp;lt; 0.05). Conclusions: The addition of cabozantinib to temozolomide offers synergistic anticancer effects in uterine sarcoma cell lines and xenograft mouse models, including PDX. These results warrant further investigation in a clinical trial.
Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages
Authors: Katja Hönzke, Benedikt Obermayer, Christin Mache, Diana Fatykhova, Mirjana Kessler, Simon Dökel, Emanuel Wyler, Morris Baumgardt, Anna Löwa, Karen Hoffmann, Patrick Graff, Jessica Schulze, Maren Mieth, Katharina Hellwig, Zeynep Demir, Barbara Biere, Linda Brunotte, Angeles Mecate-Zambrano, Judith Bushe, Melanie Dohmen, Christian Hinze, Sefer Elezkurtaj, Mario Tönnies, Torsten T. Bauer, Stephan Eggeling, Hong-Linh Tran, Paul Schneider, Jens Neudecker, Jens C. Rückert, Kai M. Schmidt-Ott, Jonas Busch, Frederick Klauschen, David Horst, Helena Radbruch, Josefine Radke, Frank Heppner, Victor M. Corman, Daniela Niemeyer, Marcel A. Müller, Christine Goffinet, Ronja Mothes, Anna Pascual-Reguant, Anja Erika Hauser, Dieter Beule, Markus Landthaler, Stephan Ludwig, Norbert Suttorp, Martin Witzenrath, Achim D. Gruber, Christian Drosten, Leif-Erik Sander, Thorsten Wolff, Stefan Hippenstiel, Andreas C. Hocke
Journal: European Respiratory Journal (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive.Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used to validate ex vivo results.We provide evidence that alveolar ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation and virus-induced tissue damage in the human alveolus. Instead, ex vivo infected human lungs and COVID-19 autopsy samples showed that alveolar macrophages were frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake and a related inflammatory and anti-viral activation, especially in "inflammatory alveolar macrophages", comparable to those induced by SARS-CoV and MERS-CoV, but different from NL63 or influenza virus infection.Collectively, our findings indicate that severe lung injury in COVID-19 probably results from a macrophage-triggered immune activation rather than direct viral damage of the alveolar compartment.
Membrane-Anchored and Tumor-Targeted IL12 (attIL12)-PBMC Therapy for Osteosarcoma
Authors: Qing Yang, Jiemiao Hu, Zhiliang Jia, Qi Wang, Jing Wang, Long Hoang Dao, Wendong Zhang, Sheng Zhang, Xueqing Xia, Richard Gorlick, Shulin Li
Journal: Clinical Cancer Research (2022)

Chimeric antigen receptor (CAR) T-cell therapy has shown great promise for treating hematologic malignancies but requires a long duration of T-cell expansion, is associated with severe toxicity, and has limited efficacy for treating solid tumors. We designed experiments to address those challenges.We generated a cell membrane-anchored and tumor-targeted IL12 (attIL12) to arm peripheral blood mononuclear cells (PBMC) instead of T cells to omit the expansion phase for required CAR T cells.This IL12-based attIL12-PBMC therapy showed significant antitumor efficacy in both heterogeneous osteosarcoma patient-derived xenograft tumors and metastatic osteosarcoma tumors with no observable toxic effects. Mechanistically, attIL12-PBMC treatment resulted in tumor-restricted antitumor cytokine release and accumulation of attIL12-PBMCs in tumors. It also induced terminal differentiation of osteosarcoma cells into bone-like cells to impede tumor growth.In summary, attIL12-PBMC therapy is safe and effective against osteosarcoma. Our goal is to move this treatment into a clinical trial. Owing to the convenience of the attIL12-PBMC production process, we believe it will be feasible.
Phase II/III Results of a Trial of Anti–Tumor Necrosis Factor Multivalent NANOBODY Compound Ozoralizumab in Patients With Rheumatoid Arthritis
Authors: Tsutomu Takeuchi, Masafumi Kawanishi, Megumi Nakanishi, Hironori Yamasaki, Yoshiya Tanaka
Journal: Arthritis & Rheumatology (2022)

To assess the efficacy and safety of subcutaneous administration of 30 mg or 80 mg of ozoralizumab plus methotrexate (MTX) in patients with rheumatoid arthritis (RA) whose disease remained active despite MTX therapy.In this multicenter, double-blind, parallel-group, placebo-controlled phase II/III trial, 381 patients were randomized to receive placebo, ozoralizumab 30 mg, or ozoralizumab 80 mg, plus MTX subcutaneously injected every 4 weeks for 24 weeks. The primary end points were the response rates based on the American College of Rheumatology 20% improvement criteria (ACR20) at week 16 and change in the Sharp/van der Heijde score (ΔSHS) from baseline to week 24.The proportion of patients with an ACR20 response at week 16 was significantly higher (P < 0.001) in both ozoralizumab groups (79.6% for 30 mg, 75.3% for 80 mg), compared with placebo (37.3%); these improvements were observed from the first week of treatment. The proportion of the patients with structural nonprogression (ΔSHS ≤0) was significantly higher in both ozoralizumab groups than in the placebo group. For some secondary end points, significantly greater improvements were observed starting from as early as day 3. Serious adverse events occurred in 4 patients in the ozoralizumab 30-mg group and 5 patients in the ozoralizumab 80-mg group.In patients with active RA who received ozoralizumab in combination with MTX, the signs and symptoms of RA were significantly reduced as compared with the outcomes in those receiving placebo. Ozoralizumab demonstrated acceptable tolerability with no new safety signals when compared with other antibodies against tumor necrosis factor.
Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex
Authors: Dieke J van Rees, Panagiota Bouti, Bart Klein, Paul J H Verkuijlen, Michel van Houdt, Karin Schornagel, Anton T J Tool, David Venet, Christos Sotiriou, Sarra El-Abed, Miguel Izquierdo, Sébastien Guillaume, Cristina Saura, Serena Di Cosimo, Jens Huober, Rebecca Roylance, Sung-Bae Kim, Taco W Kuijpers, Robin van Bruggen, Timo K van den Berg, Hanke L Matlung
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Neutrophils kill antibody-opsonized tumor cells using trogocytosis, a unique mechanism of destruction of the target plasma. This previously unknown cytotoxic process of neutrophils is dependent on antibody opsonization, Fcγ receptors and CD11b/CD18 integrins. Here, we demonstrate that tumor cells can escape neutrophil-mediated cytotoxicity by calcium (Ca 2+ )-dependent and exocyst complex-dependent plasma membrane repair. Methods We knocked down EXOC7 or EXOC4, two exocyst components, to evaluate their involvement in tumor cell membrane repair after neutrophil-induced trogocytosis. We used live cell microscopy and flow cytometry for visualization of the host and tumor cell interaction and tumor cell membrane repair. Last, we reported the mRNA levels of exocyst in breast cancer tumors in correlation to the response in trastuzumab-treated patients. Results We found that tumor cells can evade neutrophil antibody-dependent cellular cytotoxicity (ADCC) by Ca 2+ -dependent cell membrane repair, a process induced upon neutrophil trogocytosis. Absence of exocyst components EXOC7 or EXOC4 rendered tumor cells vulnerable to neutrophil-mediated ADCC (but not natural killer cell-mediated killing), while neutrophil trogocytosis remained unaltered. Finally, mRNA levels of exocyst components in trastuzumab-treated patients were inversely correlated to complete response to therapy. Conclusions Our results support that neutrophil attack towards antibody-opsonized cancer cells by trogocytosis induces an active repair process by the exocyst complex in vitro. Our findings provide insight to the possible contribution of neutrophils in current antibody therapies and the tolerance mechanism of tumor cells and support further studies for potential use of the exocyst components as clinical biomarkers.